Biochem Pharmacol. 2014 Jul 25. pii: S0006-2952(14)00420-1. doi: 10.1016/j.bcp.2014.07.014. [Epub ahead of print]
Abstract
Cannabinoids
have been shown to promote the expression of the intercellular adhesion
molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive
and antimetastatic action. Using lung cancer cell lines (A549, H460)
and metastatic cells derived from a lung cancer patient, the present
study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell
adhesion to lymphokine-activated killer (LAK) cells and LAK
cell-mediated cytotoxicity. Cannabidiol (CBD), a non-psychoactive
cannabinoid, enhanced the susceptibility of cancer cells to adhere to
and subsequently lysed by LAK cells, with both effects being reversed by
a neutralizing ICAM-1 antibody. Increased cancer cell lysis by CBD was
likewise abrogated when CBD-induced ICAM-1 expression was blocked by
specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2)
and to transient receptor potential vanilloid 1. In addition, enhanced
killing of CBD-treated cancer cells was reversed by preincubation of LAK
cells with an antibody to lymphocyte function associated antigen-1
(LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event
within this process. ICAM-1-dependent pro-killing effects were further
confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol
(THC) and R(+)-methanandamide, a stable endocannabinoid analogue.
Finally, each cannabinoid elicited no significant increase of LAK
cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B,
associated with a far less pronounced (CBD, THC) or absent
(R(+)-methanandamide) ICAM-1 induction as compared to cancer cells.
Altogether, our data demonstrate cannabinoid-induced upregulation of
ICAM-1 on lung cancer cells to be responsible for increased cancer cell
susceptibility to LAK cell-mediated cytolysis. These findings provide
proof for a novel antitumorigenic mechanism of cannabinoids.
Copyright © 2014. Published by Elsevier Inc.
Copyright © 2014. Published by Elsevier Inc.
Lysis
From Wikipedia, the free encyclopedia
This article is about the biological definition of the word Lysis. For other uses, see Lysis (disambiguation).
Lysis (/ˈlaɪsɪs/; Greek λύσις lýsis, "a loosing" from λύειν lýein, "to unbind") refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate".
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